Different effects of human neutrophil elastase on platelet glycoproteins IIb and IIIa of resting and stimulated platelets.
The effect of human neutrophil elastase (HNE) on the structure and receptor activity of platelet glycoprotein IIb/IIIa complex was studied. Resting platelets, which bound only traces of 125I-fibrinogen in the absence of ADP, were found to be barely susceptible to HNE. As shown by immunoblotting experiments, treatment of such platelets with HNE (14 micrograms/ml) did not provoke a detectable cleavage of GPIIb but resulted in a partial digestion of GPIIIa and appearance of 110 kDa fragment. Such proteolytic modification of the GPIIb/IIIa complex was accompanied by a slight increase in the binding of fibrinogen to blood platelets in the absence of ADP. Treatment of partially activated platelets (spontaneous activation during washing procedure) with HNE caused a progressive loss of GPIIb and degradation of GPIIIa to 110 kDa and 60 kDa fragments. These spontaneously stimulated platelets had initially a high number of fibrinogen binding sites exposed, corresponding to approximately 50% of receptor capacity observed in platelets activated by the optimal concentration of ADP. Digestion of GPIIb/IIIa by HNE of such platelets markedly increased the exposure of fibrinogen receptors. Thus, the stimulation of platelets increases significantly the susceptibility of the GPIIb/IIIa complex to proteolysis by HNE. However, such modification of the GPIIb/IIIa does not destroy its function as a receptor for fibrinogen either on the resting or activated platelets.
Bykowska
K
K
Laboratory of Blood Coagulation and Haemostasis, Institute of Haematology, Warsaw, Poland.
Pawlowska
Z
Z
Cierniewski
C
C
Lopaciuk
S
S
Kopeć
M
M
D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007457:Iodine Radioisotopes; D009504:Neutrophils / Q000201:enzymology*; D010196:Pancreatic Elastase / Q000097:blood*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*
D007457:Iodine Radioisotopes; D010980:Platelet Membrane Glycoproteins; D010196:Pancreatic Elastase